Haloalkyl pentahalophenyl carbonates



United States Patent 3,152,168 HALGALKYL PENTAHALOPHENYL CARBQNATES JohnK. Fincire, San Jose, Calif and Robert H. Mills,

Webster Groves, Mo., assignors to Monsanto Company, a corporation ofDeiaware No Drawing. Fiied Sept. 5, 1961, Ser. No. 135,738 8 Ciaims.(Cl. 260-463) This invention relates to a novel class of derivatives ofpentahalophenol. More particularly, this invention is concerned with aclass of new organic compounds which are haloalkyl and haloalkenylpentahalophenyl carbonates. Such carbonates have been found to possessuseful and unexpected biological activity.

The novel compounds of this invention have the formula where X isselected from chlorine and bromine, Y is selected from chlorine andbromine, n is an integer from 1 to 4, and R is selected from saturatedacyclic hydrocarbon radicals and mono-oiefinically unsaturated acyclichydrocarbon radicals containing from 2 to 6 carbon atoms. It will beapparent that, depending upon the value of n, the radicals representedby R will be di, tri, tetra or pentavalent. Illustrative of suchsaturated and unsaturated acyclic hydrocarbon radicals are a i H CBXSONBYHROCCI CsXaOcORYn NaCl Two other methods which are employed to producethe compounds of this invention involve the reaction of a chloroformatewith either an alcohol or a pentahalophen- 01. In each of these latterpreparations it is preferred to add a tertiary amine to the reactionmixture. Such an amine serves as an acceptor for hydrogen chloride whichforms during the reaction. Illustrative of the tertiary amines which canbe used are trimethylamine, triethylamine, dimethylaniline,diethylaniline, pyridine, picoline, quinoline, lutidine, and the like.The reactions employing an amine acceptor are shown in the followingequations:

II CeX5O 00BX11 (C2115) aN-HC l In practicing the preparations ofEquations b and c, it is also preferred to use an inert organic solventfor the pentahalo starting material. Among the suitable solvents arebenzene, toluene, xylene, hexane, heptane, octane, dipropyl ether,diethyl ether, tetrahydrofuran, dioxane and the like.

It should be noted that, although both are preferred, neither thetertiary amine nor the inert organic solvent are essential to thepreparation of the compounds of this invention. In the absence of suchan amine, the hydrogen chloride which forms during the reaction can beboiled ofi.

Employing any of the above methods of preparation, the reactiontemperature will depend primarily upon the particular reactants whichare selected. Said temperature can vary from room temperature to thereflux temperature of the system.

The invention will be more fully understood by reference to thefollowing examples. These examples, however, are given for the purposeof illustration only and are not to be construed as limiting the scopeof the present invention in any way.

EXAMPLE I A suitable reaction vessel is charged with 26.6 grams (0.]mole) of pentachlorophenol dissolved in ml. of toluene at 30 C. Thesolution is stirred while 15.7 grams (0.1 mole) of 3-chloropropylchloroformate is added. The stirring is continued, and 10.1 grams (0.1mole) of triethylamine in 25 ml. of toluene is added dropwise over aperiod of about 20 minutes. The temperature rises to 45 C. during theaddition of the amine, and the mixture is then further stirred andheated to 110 C. for about 6 hours. The reaction mixture is cooled, andthe amine hydrochloride which forms is filtered off and washed withtoluene. The toluene is removed from the combined washings and filtrateleaving an amber EXAMPLE II A suitable reaction vessel is charged with31.3 grams (0.1 mole) of sodium pentachlorophenate dissolved in ml. ofwater. There is then added 1.0 gram of activated charcoal and 1.0 gramof dicalite speed plus. The mixture is filtered, and the filtrate iscooled to about 3 C. The mixture is stirred while 14.3 grams (0.1 mole)of 2-chloroethyl chloroformate is added dropwise over a period of 1hour. The resulting mixture is stirred for an additional hour while thetemperature rises to about 20 C. It is then filtered, washed severaltimes with water, and dried by distillation for 30 minutes at about 95C. with a water aspirator to give an essentially quantitative yield ofcrude product. It is mixed with activated charcoal oil dicalite speedplus and filtered to yield an oily product which solidifies. Saidproduct is triturated to obtain 21.3 grams of Z-ehloroethylpentachlorophenyl carbonate as a powder, MP. 70-76 C. Recrystallizationfrom Skellysolve B (an essentially n-hexane solvent having a boilingrange of 6070 C.) and methylcyclohexane raised the melting point to82-83 C. Analysis shows 57.0% of chlorine as against a calculated valueof for C9H4C16O3.

EXAMPLE III A suitable reaction vessel is charged with 24.4 grams (0.05mole) of pentabromophenol suspended in 175 ml. of toluene at 30 C. 7.15grams (0.05 mole) of 2-chloroethyl chloroformate is added with stirring.The stirring is continued, and a solution of 5.1 grams (0.05 mole) oftriethylamine in 25 ml. of toluene is added dropwise over a period of 20minutes while the temperature rises to about 38 C. The mixture is thenheated at 110 C. for about 6 hours. The reacted mixture is filtered toremove the amine hydrochloride which forms, and the latter is washedwith toluene. The toluene is removed from the combined washings andfiltrate leaving a pale yellow solid. Said solid is recrystallized frommethylcyclohexane with activated charcoal, and then recrystallized againfrom methylcyclohexane. There is obtained 22.1 grams of 2-chloroethylpentabromophenyl carbonate as pale yellow crystals, Ml. 130131 C.Analysis shows 7.1% of chlorine as against a calculated value of 5.96%for A suitable reaction vessel is charged with 16.4 grams (0.05 mole) ofpentachlorophenyl chloroforrnate dissolved in 150 ml. of Skellysolve C.The solution is stirred while 7.5 grams (0.05 mole) of2,2,2-trichloroethanol is added. The stirring is continued while 5.1grams (0.05 mole) of triethylamine in 25 ml. of Skellysolve C is addeddropwise over a period of 20 minutes. The resultant mixture is heated atreflux temperature for about 6 hours, after which it is worked up in themanner described in Example Ill. There is obtained 10.6 grams of2,2,2-trichloroethyl pentachlorophenyl carbonate as white crystals, MP.110l11 C. Analysis shows 64.3% of chlorine as against a calculated valueof 64.21% for C H Cl O EXAMPLE V A suitable reaction vessel is chargedwith 16.4 grams (0.05 mole) of pentachlorophenyl chloroformate dissolvedin 150 ml. of Skellysolve C. The solution is stirred while 6.3 grams(0.05 mole) of 2-brornoethanol in 50 ml. of benzene is added. Thestirring is continued while 51 grams (0.05 mole) of triethylamine in 25ml. of henzene is added dropwise over a period of 20 minutes. Theresultant mixture is heated at reflux temperature for about 6 hours,after which it is worked up in the manner described in Example 111.There is obtained 5.1 grams of 2-bromoethyl pentachlorophenyl carbonateas white crystals, M.P. 91-92 C. Analysis shows 41.9% of chlorine asagainst a calculated value of 42.48% for C9H4BI'C1503 EXAMPLE VI Asuitable reaction vessel is charged with 16.4 grams (0.05 mole) ofpentachlorophenyl chloroforrnate dissolved in 150 ml. of Skellysolve C.The solution is stirred while 5.4 grams (0.05 mole) of 4-chlorobutanolin 75 ml. of benzene is added. The stirring is continued while 5.1 grams(0.05 mole) of triethylarnine in 25 ml. of ben- 6i. zone is addeddropwise over a period of 25 minutes. The resultant mixture is stirredat room temperature for about 12 hours, and the amine hydrochloridewhich forms is filtered off and washed with benzene. The washings andfiltrate are combined, and the solvents are removed. A pale yellow oiland a white solid material remain. After filtration through a sinteredglass funnel, the filtrate is distilled. The solid residue in thedistillation flask is recrystallized from Skellysolve B and activatedcharcoal,

and recrystallized again from Skellysolve B. There is obtained 2.1 gramsof 4-chl0robutyl pentachlorophenyl carbonate as white crystals, MP. 6970C. Analysis shows 53.2% of chlorine as against a calculated value of53.06% for C H CI O EXAMPLE VII A suitable reaction vessel is chargedwith 16.4 grams (0.05 mole) of pentachlorophenyl chloroforrnatedissolved in 150 ml. of Skellysolve C. The solution is stirred while 6.5grams (0.05 mole) of 2,3-dichloropropatrol in 50 ml. of benzene isadded. The stirring is continued while 5.1 grams (0.05 mole) oftriethylamine in 25 ml. of Skellysolve C is added dropwise over a periodof 3-0 minutes. The resultant mixture is heated at reflux temperaturefor about 6 hours, after which it is worked up in the manner describedin Example III. There is obtained 3.4 grams of 2,3-dichloropropylpentachlorophenyl carbonate as a white solid, MP. 7577 C. Analysi shows5 8.6% of chlorine as against a calculated value of for C1QH5C17O3.

EXAMPLE VlII A suitable reaction vessel is charged with 16.4 grams (0.05mole) of pentachlorophenyl chloroformate dissolved in 150 ml. ofanhydrous ether. The solution is stirred while 4.7 grams (0.05 mole) of1-chloro-2-propanol is added. The stirring is continued while a solutionof 4.0 grams (0.05 mole) of pyridine in 25 ml.

of ether is added dropwise over a period of 20 minutes- The resultantmixture is heated to about 35 C. and stirred at that temperature for 6hours. It is then worked up in the manner described in Example IIIexcept that the recrystallization is from pentane. There is obtained 3.2grams of l-(chloromethyDethyl pentachlorophenyl carbonate as whitecrystals, M.P. 6465 C. Analysis shows 55.1% of chlorine as against acalculated value of 54.99% for C H Cl O EXAMPLE IX A suitable reactionvessel is charged with 16.4 grams (0.05 mole) of pentachlorophenylchloroformate dissolved in 150 ml. of toluene. The solution is stirredwhile 6.45 grams (0.05 mole) of 1,3-dichloro-2-propanol is added. Thestirring is continued while 4.0 grams (0.05 mole) of pyridine in 25 ml.of toluene is added dropwise over a period of 30 minutes. The resultantmixture is heated to C. and stirred at that temperature for about 3hours. It is then Worked up in the manner described in Example VI toyield 9.1 grams of 2-chloro-1-(chloromethyl)ethyl pentachlorophenylcarbonate as white crystals, MP. 122123 C. Analysis shows 58.8% ofchlorine as against a calculated value Of fOl' C1QH5CI7O3.

EXAMPLE X A suitable reaction vessel is charged with 109.6 grams (0.33mole) of pentachlorophenyl chloroformate. There is then added 53.6 grams(0.67 mole) of Q-chloroethanol. The reactants are stirred and heatedslowly to about 129 C. over a period of 2 /2 hours. Hydrogen chloride isevolved during most of the heating period, the rate of evolutionbecoming very slow at the end of said period.

The reaction mixture is then cooled and poured into water. The solidmaterial is filtered from the water after which the former is tituratedand washed with water. It is then air dried for two hours. This crudeproduct is recrystallized twice from methanol to yield 99.9 grams ofZ-chloroethyl pentachlorophenyl carbonate, M.P. 81- 82 C. Analysisshowed 57.0% of chlorine as against a cflculated value of 57.06% for C HCl O Following the procedures outlined in the preceding examples, theother pentahalophenyl derivatives of this invention are readilyprepared. Such other derivatives include 2-bromo-l-(bromomethyl)ethylpentachlorophenyl carbonate, l,2,2,2-tetrachloroethyl pentachlorophenylcarbonate, 3-bromopropyl pentabromophenyl carbonate, 3,3-dichloro-Z-propenyl pentachlorophenyl carbonate, 2-bromo-l,1-dimethylpropyl pentachlorophenyl carbonate, 2-chloropentylpentabromophenyl carbonate, 1,1-dirnethyl-2,2,2-trichloroethylpentachlorophenyl carbonate, 5- brorno-l-methylpentyl pentachlorophenylcarbonate, 2- bromo-l-methylpropyl pentabromophenyl carbonate, 3-chloro-Z-propenyl pentachlorophenyl carbonate,l-dichloromethyl-l-ethylpropyl pentachlorophenyl carbonate, 2,2-dichloro-l-(dichloromethyl)ethyl pentachlorophenyl carbonate,6-chlorohexyl pentabromophenyl carbonate, 2- chloro-3-butenylpentachlorophenyl carbonate and the like.

As noted above, the pentahalophenyl carbonates of this invention havebeen found to display useful and unexpected biological activity. In thisregard it should be pointed out that the chloroalkyl pentachlorophenylcarbonates are particularly preferred.

Although related compounds, such as an unsubstituted alkylpentachlorophenyl carbonate, are known, the corre sponding chloroalkylcompound demonstrates unusual superiority in its effectiveness againstbacteria and fungi coupled with an unexpectedly lower toxicity. In orderto illustrate these desirable features of the compounds of thisinvention, various tests have been made and the data obtained ishereinafter presented.

Test A To show the control of bacteria, a number of cotton swatches werewashed in a manner similar to a standard home washing machine cycle. Acommercially available anionic laundry detergent was used in this test.Swatch No. 1 was washed with said detergent mixed with 2- chloroethylpentachlorophenyl carbonate. Swatch No. 2 was washed with said detergentmixed with ethyl pentachlorophenyl carbonate. Swatch No. 3 was washedwith the detergent alone and serves as a control.

After the washing each swatch was inoculated with 2.4 1O Staphylococcusaurezzs and incubated for 24 hours. The swatches Were then rinsed withwater, and aliquots of said water were plated out in nutrient agar. Thealiquots were incubated for 48 hours, and a bacterial count was taken.The results are tabulated below:

Percent Compound in Detergent Swatch No.

loco

Test B To show the control of fungi, swatches were prepared in the samemanner at Nos. 1 and 2 in Test A. Each swatch was inoculated with2.0)(10 Aspergillus niger spores in 2 ml. of Sabourauds dextrose broth.The

swatches were then incubated at 28 C. for 7 days and checked for growth.The results are tabulated below:

Percent Compound in Detergent Swatch No.

No growth.

1 No growth. 2 Growth.

Test C One of the compounds of this invention, 2-chloroethylpentachlorophenyl carbonate, and the corresponding ethylpentachlorophenyl carbonate were tested on rabbits to obtain data withregard to toxicity. In the skin absorption test, it was found that the2-chloroethyl compound showed a MLD of greater than 3160 mg. 1 kg. andless than 5010 mg. 1 kg. On the other hand, the corresponding ethylcompound was found to be about three times more toxic. Further, the2-chloroethyl compound was found to be only a slight eye irritant whilethe corresponding ethyl compound caused marked redness with lacrimation.

It will be obvious to those skilled in the art that many modificationsand variations may be made within the scope of the present inventionwithout departing from the spirit thereof.

The embodiments of the invention in which an exelusive property orprivilege is claimed are defined as follows:

1. A compound of the formula X where X is selected from the groupconsisting of chlorine and bromine, Y is selected from the groupconsisting of chlorine and bromine, n is an integer from 1 to 4, and Ris selected from the group consisting of saturated acyclic hydrocarbonradicals and mono-olefinically unsaturated acyclic hydrocarbon radicalscontaining from 2 to 6 carbon atoms.

2. A compound of the formula References Cited in the file of this patentUNITED STATES PATENTS Honk Nov. 4, 1947 Baumgartner Sept. 18, 1951Stevens Apr. 2, 1957 OTHER REFERENCES Wagner and Zook: Synthetic OrganicChemistry." pages 483-4 (1953).

1. A COMPOUND OF THE FORMULA